tbuckley/cabot-search huggingface dataset:
Abstract 9576: Trends and Outcomes of Sudden Cardiac Arrest in Diabetes Patients With STEMI in the US
Authors: Omar Mhaimeed, SOHA DARGHAM, jassim al suwwaidi, Hani Jneid, Charbel Abi Khalil
Journal: Circulation (2022)

Introduction: Sudden cardiac arrest is a serious ST-elevation myocardial infarction (STEMI) complication.Objective: We aimed to assess the impact of diabetes on sudden cardiac arrest (SCA) in patients hospitalized with STEMI and analyzed the recent cardiovascular and socioeconomic temporal trends in those patients. Methods: We used the National Inpatient Sample (2005-2017) data to identify adult patients admitted with STEMI as the primary diagnosis. The secondary diagnosis was sudden cardiac arrest. Diabetes was used as comorbidity. The primary outcome was in-hospital death. Secondary outcomes included ventricular tachycardia (VT), ventricular fibrillation (VF), atrial fibrillation (AF), cardiogenic shock (CS), stroke, acute renal failure (ARF), and the revascularization strategy. Socioeconomic outcomes consisted of the length of stay (LoS) and total charges/stay. Results: The number of STEMI patients experiencing a SCA significantly increased from 2005 to 2017, and the mean age of participants decreased from 68 (11) to 66 (10) years old (p=0.003). While a temporal increase in risk factors was observed, mortality decreased from 65.7% to 48.6% (p&lt;0.001). However, VT, VF, AF, CS, stroke, and ARF followed an upward trend. Compared to non-diabetic patients, those with diabetes were older and more likely to be females and blacks. They had a higher risk of mortality, ARF, and pacemaker requirements (adjusted OR = 1.72 [1.68-1.83], 1.52 [1.43-1.63], 1.19 [1.06-1.34], respectively), but not stroke, VT, VF or AF. Those patients were less likely to have PCI (OR = 0.70 [0.66-0.73] and more likely to have CABG (OR = 1.18 [1.07-1.30]). Total charges/stay increased by almost 2.5-fold in all STEMI patients who develop SCA, but diabetes was associated with higher charges; no difference in the LoS was noted. Conclusion: The recent temporal trend of SCA in patients with STEMI and diabetes shows a steady decline in mortality. Diabetes patients in STEMI patients who develop a SCA have a higher likelihood of mortality and other adverse outcomes when compared to those without diabetes.
Abstract 9544: <i>PRDM16</i> Loss in 1p36 Deletion Syndrome is Associated With Worse Cardiovascular Outcomes: A Multi-Institutional Registry Study
Authors: Ryan J Kramer, Nima Fatahian, Alice Chan, Jeffrey Mortenson, Jennifer Osher, Bo Sun, Lauren E Parker, Michael Rosamilia, Sage L Atkins, Jill A Rosenfeld, Alona Birjiniuk, Edward Jones, Taylor S Howard, Hugh D Allen, Jeffrey J Kim, Daryl A Scott, Seema Lalani, Omid T Rouzbehani, Marissa A Hathaway, Jennifer L Cohen, Yukiko Asaki, Hugo R Martinez, Sihem Boudina, Andrew P Landstrom
Journal: Circulation (2022)

Introduction: 1p36 deletion syndrome can confer a predisposition to pediatric-onset cardiomyopathy. 1p36 deletion breakpoints are variable and can delete PRDM16 , a cardiac transcription factor. Early studies suggest PRDM16 loss may underlie cardiomyopathy in patients with 1p36 deletion; however, the prognostic impact of PRDM16 loss is unknown. Hypothesis: Deletion of PRDM16 in 1p36 deletion syndrome (“ PRDM16 deleted”) is associated with the development of cardiomyopathy and adverse cardiovascular outcomes. Methods: This registry study included Duke University Hospital, Texas Children’s Hospital, Primary Children’s Hospital, &amp; Le Bonheur Children’s Hospital. Standard descriptive statistics and Kaplan-Meier estimates were generated. The composite primary outcome was freedom from death, cardiac transplantation, or ventricular assist device (VAD) implantation. A cardiac-specific conditional Prdm16 knockout mouse ( Prdm16 cKO) was generated. Echocardiography, qPCR, and fibrotic staining were performed at 29 weeks. Results: 66 individuals met the inclusion criteria of 1p36 deletion syndrome and at least one clinical encounter. Among individuals with PRDM16 deleted, 37.9% developed cardiomyopathy versus 4.3% of individuals with PRDM16 not deleted (p=0.09). The most common cardiomyopathies in individuals with PRDM16 deleted were LVNC (27.6%) and DCM (13.8%). Individuals with PRDM16 deleted had a 65% probability of developing systolic dysfunction by age 18. Notably, PRDM16 deletion was associated with a significantly increased risk of death, cardiac transplant, or VAD (p=0.04) versus those with PRDM16 not deleted. Prdm16 cKO mice exhibited an increased risk of mortality (p=0.05) and decreased ejection fraction (p&lt;0.01). Prdm16 cKO mice demonstrated significantly increased cardiac fibrosis (p&lt;0.0001), and Tgf-β and Nppb mRNA were significantly upregulated (p&lt;0.05). Conclusions: PRDM16 deletion as part of 1p36 deletion syndrome confers a significantly increased risk of cardiac mortality. Murine models of cardiomyocyte Prdm16 loss demonstrate an increased risk of mortality and cardiomyopathy development. Patients with 1p36 deletion syndrome should be assessed for cardiac disease, particularly those with PRDM16 deletions.
Abstract 9553: Sirtuin1 Aggravates Hypertrophic Heart Failure Caused by Pressure Overload via Shifting Energy Metabolism
Authors: Meredith Krause-Hauch, Van Le, Linda Ines I Zoungrana, Hao Wang, Migdalia Iglesias, Di Ren, Ji Li
Journal: Circulation (2022)

Introduction: Sirtuin1 (SIRT1) serves as a deacetylase to regulate cardiac substrate metabolism during physiological and pathological conditions. The alteration in metabolic homeostasis plays a critical role in hypertrophic heart failure. Hypothesis: Cardiomyocyte SIRT1 modulates substrate metabolism to regulate cardiac remodeling during pressure overload-induced heart failure. Methods: The inducible cardiomyocyte specific Sirt1 knockout (icSirt1 -/- ) and its wild type littermates (Sirt1 f/f ) C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery to induce pressure overload. The cardiac functions were evaluated with echocardiography and electrocardiography measurements. Results: The pressure overload by TAC induces upregulation of cardiac SIRT1 in Sirt1 f/f but not icSirt1 -/- mice. The cardiac contractile dysfunctions caused by TAC-induced pressure overload occurred in Sirt1 f/f but not in icSirt1 -/- mice. Intriguingly, Sirt1 f/f heart showed a drastic reduction in systolic contractility and electric signals during post-TAC surgery, whereas icSirt1 -/- heart demonstrated significant resistance to the pathological stress by TAC-induced pressure overload as evidenced by no significant changes in systolic contractile functions and electric properties. The Seahorse data revealed that TAC-induced pressure overload causes a decrease in basal respiration and ATP generation, as well as reduced OXPHOS (oxidative phosphorylation) integrity of mitochondria in Sirt1 f/f but not in icSirt1 -/- cardiomyocytes. The targeted proteomics showed that the pressure overload trigged downregulation of the SIRT1-associated IDH2 (isocitrate dehydrogenase 2) that result in an increased oxidative stress in mitochondria. Moreover, a significant alteration in substrate metabolism was observed in Sirt1 f/f but not in icSirt1 -/- heart in response to TAC-induced pressure overload stress. Conclusions: SIRT1 interferes metabolic homeostasis through regulating mitochondrial IDH2 during pressure overload. Inhibition of SIRT1 activity benefits cardiac functions under pressure overload-related pathological conditions. SIRT1 antagonism could be a pharmacological approach for hypertrophic heart failure patients.
Abstract 9472: Effects of Social Determinants of Health on ICD Shocks, Hospitalizations, &amp; Mortality in the First Year After an ICD
Authors: Megan M Streur, Jonathan P Auld, Elizabeth Frazier, Wei-Lun Chang, Fatemeh M Choupani, Ana C Liberato, ka yee kwan, Tao Zheng, Frances Elaine Thompson, Cynthia M Dougherty
Journal: Circulation (2022)

Introduction: Disparities in the receipt of an implantable cardioverter defibrillator (ICD) have been reported. African Americans (AA), women, and those with lower SES are less likely to receive an ICD and more likely to report poor outcomes after ICD implant. The purpose of this study was to determine if social determinants of health (SDOH) were associated with the number of ICD shocks experienced, all cause hospitalization, or mortality in the first year following receipt of an initial ICD. Hypothesis: SDOH (age, race, biological sex, annual income, employment, education, rural vs urban locale) are related to total ICD shocks, all cause hospitalization, and mortality in the first year after an initial ICD. Methods: 301 patients who received an initial ICD (58% primary prevention, 42% secondary prevention) were followed for 1 year. Patients were 64 ± 2 years old, 91% Caucasian, 4% AA, 2% Am Indian (AI), 2% Latinx, 74% male, 87% urban , 65% retired-disabled, 45% household income &lt; $50K, and 48% high school education or less. ICD shocks, hospitalizations, &amp; deaths were verified using the EMR. Descriptive statistics, correlations, and multivariate logistic regression were used to examine for SHOD related disparities in health outcomes over 1 year. Results: There were no significant associations between SDOH and ICD shocks, all cause hospitalization, or mortality over 1 year. ICD shocks : 34 patients (11.3%) had at least 1 ICD shock over 12-months of follow-up. The number of ICD shocks was higher for those who engaged in hazardous drinking (25%: 5% women, 20% men, p=0.03), and those who received an ICD for secondary prevention (primary 8.4%, secondary 15.4% (p=0.04) at baseline.. Hospitalization : 95 patients (31.6%) were hospitalized over the 12 months of follow-up. Mortality : 9 (3%) deaths (67% cardiac related) were recorded over the 12 months, with no associations found between SDOH and mortality. Conclusions: SDOH were not associated with the incidence of ICD shocks, all-cause hospitalization, or mortality in the first year after receipt of an initial ICD. SDOH influences on access to receipt of an initial ICD may have contributed to the observed outcomes post-ICD.
Abstract 9727: Reduced Bmpr2 Causes a Decrease in Foxf1 That Links Unrepaired DNA Damage to Persistent Pulmonary Hypertension
Authors: Sarasa Isobe, Ramesh V Nair, Jan-Renier A Moonen, Lingli Wang, Jakob Koerbelin, Michael Snyder, Marlene Rabinovitch
Journal: Circulation (2022)

Introduction: B MPR2 mutation is the most common genetic cause of pulmonary arterial hypertension (PAH). Loss of BMPR2 causes pulmonary arterial (PA) endothelial cell (EC) dysfunction and impairs EC-mediated suppression of smooth muscle cells proliferation. These are characteristic features of PAH vascular cells as is the presence of DNA damage that can be induced by oxidative stress. We previously showed that EC- Bmpr2 -/- mice have persistent pulmonary hypertension (PH) with reoxygenation after hypoxia. However, the role of DNA damage in causing persistent PH related to loss of BMPR2 and oxidative stress is unknown. Hypothesis: We hypothesize that loss of BMPR2 causes unrepaired DNA damage and persistent PH by altering the expression of genes that maintain EC homeostasis. Methods and Results: DNA damage assessed by γH2AX foci was observed in PAEC of EC- Bmpr2 -/- mice in room air, that was more extensive after reoxygenation (10% hypoxia for 3 weeks followed by recovery in room-air for 4 weeks). Deletion of the DNA damage sensor ataxia-telangiectasia mutated (ATM) in EC of mice (EC- Atm -/- ) also resulted in persistent DNA damage and PH. RNA sequencing of PAEC after reoxygenation in EC- Bmpr2 -/- and EC- Atm -/- mice vs. controls showed downregulated EC differentiation and development genes enriched in biding motifs for Foxf1, a transcription factor associated with DNA repair and angiogenesis. Foxf1 expression was reduced in PAEC with loss of BMPR2 or ATM. Loss of Foxf1 decreased angiogenic genes Cldn5 and Vegfr2 , and DNA damage response genes Atm and p53 , and impaired PAEC migration and tube formation. Foxf1 overexpression increased these genes in PAEC. Immunohistochemistry showed decreased FOXF1 in PAEC of human pulmonary vascular lesions. Delivery of Foxf1 to EC- Bmpr2 -/- mice with an AAV2-peptide targeting the PA endothelium attenuated DNA damage in PAEC, restored angiogenesis genes and completely reversed persistent PH returning right ventricular systolic pressure to normal levels. Conclusions: We link loss of BMPR2 and DNA damage sensing in PAEC to persistent DNA damage and PAH and show that both are mediated by reduced FOXF1 . In EC- Bmpr2 -/- mice, Foxf1 gene therapy attenuated DNA damage restored angiogenesis genes, and prevented persistent PH.
Abstract 9688: Isoproterenol Assisted Differentiation Between Sludge and Organized Thrombus of Left Atrial Appendage to Help Guide Percutaneous Closure
Authors: Syed A Hyder, Sandeep Goyal, Mani Vannan, Shizhen Liu
Journal: Circulation (2022)

Background: Percutaneous left atrial appendage (LAA) closure is contraindicated in patients with LAA thrombus. It can be challenging to distinguish slow flow (sludge) from organized thrombus on echocardiography. Recent case reports have shown that isoproterenol infusion can distinguish LAA sludge from thrombus, however, no mid/long-term outcome data exists. Methods: A retrospective study was conducted on 32 patients who underwent Watchman™ implantation at Piedmont Atlanta Hospital during 2021. Patients were divided into two groups, 1) clear LAA [Standard] and 2) suspected LAA thrombus versus sludge [Sludge]. The Sludge group underwent isoproterenol infusion prior to implantation of Watchman™ device. Data gathered included demographics, medical history, procedural data, and 6-months outcomes defined as TIA, CVA, or device related thrombus. Chi-square and T-test was used for statistical analysis. Results: The cohort had 8 patients (25%) in Sludge group with remaining 24 patients (75%) in Standard group. The Sludge group was younger at 73.5 years compared to 77.0 years for Standard group [p=0.02]. Other baseline characteristics including sex, comorbidities, and history of prior TIA/CVA were similar among both groups. Median CHA 2 DS 2 VASc Score was 5.0 for Standard and 4.5 for Sludge group [p= 0.21]. All patients in Sludge group had successful clearance with isoproterenol; median dose required was 6 mcg. LAA dimensions were similar with the median device size being 27 mm for both groups [p= 0.343]. At 45-day follow-up, one patient in Standard group had device related thrombus; it resolved on subsequent scan. At 6-months, one patient in Sludge group had experienced TIA; no patients underwent CVA. Conclusions: LAA thrombus is an absolute contraindication for percutaneous LAA device implantation, however, it can be difficult to differentiate between sludge and organized thrombus. This study demonstrates that intraprocedural isoproterenol infusion can be used to clear LAA sludge by improving LV contractility. No significant difference in mid-term outcomes was observed in our study groups, suggesting that isoproterenol assisted differentiation of LAA sludge from thrombus may allow successful LAA closure in cases that are deemed to have LAA sludge.
Abstract 9692: Sex Differences in Cardiovascular Outcomes of SGLT-2 Inhibitors in Heart Failure Randomized Controlled Trials: A Systematic Review and Meta-Analysis
Authors: Frederick Rivera, Jem Marie Golbin, Marie Francesca M Ansay, Aubrey Melody R Rocimo, Pia Gabrielle I Alfonso, Bradley Ashley G Ong, Marianne Katharina Taliño, Deogracias De Luna, Peter A McCullough, Annabelle Santos Volgman
Journal: Circulation (2022)

Background: Randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing major adverse cardiovascular events (MACE) in patients with heart failure. A recently published meta-analysis showed that the use of SGLT-2i among women with diabetes resulted in less reduction in MACE vs. men. This study aims to determine sex differences in MACE in patients with chronic heart failure. Methods: We systematically searched the medical database until April 30, 2022, and retrieved all the RCTs using SGLT-2is with specified CV outcomes. We used PRISMA, Preferred Reporting Items for a Review and Meta-analysis. We pooled the hazard ratio (HR) of MACE in both sexes, did a meta-analysis, and analyzed the odds ratio (OR) of MACE based on sex. Statistical analysis was completed with the use of Cochrane Review Manager (RevMan) version 5.4. Results of the pooled hazard ratio (HR) and the 95% confidence interval (CI) were made based on intention-to-treat analysis. Results: Figure 1 shows the results of the meta-analysis of 4 RCTs conducted with SGLT-2is (n=20725) vs. placebo. MACE was significantly lower in males and females taking SGLT-2is (men - HR 0.76; 95% CI 0.69 to 0.83; p=0.00001; women - HR 0.72; 95% CI 0.63 to 0.83; p=0.00001). Pooled data from three of the RCTs (n=7233) revealed a greater reduction in MACE in females vs. males (OR 1.32; 95% CI 1.14 to 1.53; p=0.0002). Conclusion: SGLT-2is reduce the risk of MACE in patients with heart failure, regardless of sex. However, the benefits were more pronounced in females, contrary to the meta-analysis of SGLT-2is in patients with diabetes. This finding may reflect an actual sex difference due to physiologic or behavioral factors or can be due to inadequate statistical power. More sex-based RCTs may help establish these sex differences in cardiovascular outcomes.
Abstract 9710: Prevalence of Ekg Criteria Suggestive of Fabry’S Disease in Heart Failure Patients
Authors: Al-Ameen Oredegbe, Casey White, Mohammed Mustafa, George Tawfellos, Erin Harris, Mikhail Torosoff
Journal: Circulation (2022)

Introduction: Cardiac disease is the most important cause of morbidity and mortality in Fabry disease, an X-linked genetic condition caused by a defect in alpha-galactosidase A. Diagnosis of Fabry’s disease requires high index of suspicion and includes EKG assessment. Prevalence of EKG changes consistent with Fabry disease in patients admitted with heart failure has not been well investigated. Methods: Clinical, EKG and echocardiographic data were collected in 460 non-V paced consecutive CHF patients enrolled over 2 years in the Get with The Guidelines Heart failure (GWG-HF) registry at a single academic center. Fabry disease EKG features including shortened PR intervals, AV block, LVH criteria, QRS prolongation, left atrial enlargement (LAE), atrial fibrillation (AFIB), and bradycardia were recorded. Results: Of the studied criteria, shortened PR was noted in only 1.85% (6/324) of patients in sinus rhythm. Of the 460 non-V-paced rhythms patients, LVH was noted in 19% (87/460), QRS&gt;120 ms in 20% (96/460), LAE in 21% (98/460), AFIB in 21% (100/460), and HR &lt;60 bpm in 8% (37/460). Overall, 15% (70/460) of patients with non-V-paced rhythms had a combination of LVH/QRS and LAE/AFIB; this combination of ECG findings is potentially suggestive of Fabry disease. There were no significant differences in gender, age, BMI, BNP, GFR, or Hgb levels, degree LV dysfunction, histories of HTN, CAD, diabetes in these 70 patients vs. the rest of the cohort. However, patients with these criteria had significantly increased prevalence of HFrEF (55.7%, 39/70, vs. 42.8% in the rest of the cohort, 167/390, p=0.031). There was no difference in re-admission and/or mortality rates during the 70.7+/-25.2 month follow-up according to these ECG criteria. Conclusions: In our study of unselected patients with ascertained CHF diagnosis, many manifested with multiple EKG features associated with Fabry’s disease. While these patients had increased prevalence of HFrEF, there were no clinical or demographic characteristics separating these individuals from the rest of the cohort. Given poor prognosis and treatable nature of Fabry’s disease, these patients may benefit from additional clinical and laboratory evaluation directed at Fabry’s disease diagnosis
Abstract 9535: The Effect of Vascular Smooth Muscle Cell miR-33a Expression on apoAI-Mediated Cholesterol Efflux and Macrophage-Like Cell Transdifferentiation
Authors: Ikechukwu Esobi, Olanrewaju Oladosu, Jing Echesabal-Chen, Rhonda Powell, Terri Bruce, Alexis D Stamatikos
Journal: Circulation (2022)

Background: ABCA1 removes cellular cholesterol by participating in apoAI-mediated cholesterol efflux. MiR-33a is an SREBP-2 intronic miRNA that silences ABCA1, which impairs ABCA1-dependent cholesterol efflux. Thus, miR-33a expression may be atherogenic and previous data suggests inhibiting miR-33a in certain cells is atheroprotective. However, current data is scant on whether miR-33a expression in vascular smooth muscle cells (VSMC) is atherogenic. Moreover, cholesterol accumulation in VSMC results in these cells to transdifferentiate into an atherogenic macrophage-like cell (MLC). Therefore, ablating miR-33a expression in VSMC may be atheroprotective via hindering cholesterol accumulation and MLC transdifferentiation in these cells by enhancing apoAI-mediated cholesterol efflux. Methods: An immortalized VSMC line MOVAS cells were used to generate miR-33a knockout (KO) MOVAS cells via using CRISPR/Cas9. We used these cells and parental wild-type (WT) MOVAS cells in our studies to assess whether apoAI-mediated cholesterol efflux is increased in MLC of VSMC origin when miR-33a expression is ablated. We also analyzed whether miR-33a ablation rapidly restores VSMC phenotype in MLC of VSMC origin when cholesterol-loaded cells were exposed to apoAI. Results: We used PCR to confirm that miR-33a was deleted in miR-33a KO MOVAS cells. We also showed that miR-33a-5p and miR-33a-3p expression was absent in miR-33a KO MOVAS cells via RT-PCR. SREBP-2 functionality remained intact in miR-33a KO MOVAS cells, as determined by upregulation of SREBP-2 target genes in serum-starved conditions. When we cholesterol-loaded miR-33a KO MOVAS cells to induce MLC transdifferentiation, we observed increased apoAI-mediated cholesterol efflux when compared to WT MOVAS cells exposed to the same conditions. Based on RT-qPCR analysis, we also observed a rapid restoration in VSMC phenotype when cholesterol-loaded miR-33a KO MOVAS cells were incubated with apoAI when compared to WT MOVAS cells treated with the same conditions. Conclusions: MiR-33a expression in VSMC appears to promote MLC transdifferentiation by impairing apoAI-mediated cholesterol efflux. Future studies are underway to determine if these effects are mediated by miR-33a-5p and/or miR-33a-3p.